Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Center for Microbial Pathogenesis, Pittsburgh, PA, USA.
Sci Adv. 2019 Mar 6;5(3):eaau4255. doi: 10.1126/sciadv.aau4255. eCollection 2019 Mar.
Recent worldwide outbreaks of enterovirus 71 (EV71) have caused major epidemics of hand, foot, and mouth disease with severe neurological complications, including acute flaccid paralysis. EV71 is transmitted by the enteral route, but little is known about the mechanisms it uses to cross the human gastrointestinal tract. Using primary human intestinal epithelial monolayers, we show that EV71 infects the epithelium from the apical surface, where it preferentially infects goblet cells. We found that EV71 infection did not alter epithelial barrier function but did reduce the expression of goblet cell-derived mucins, suggesting that it alters goblet cell function. We also show that the intestinal epithelium responds to EV71 infection through the selective induction of type III interferons (IFNs), which restrict EV71 replication. Collectively, these findings define the early events associated with EV71 infections of the human intestinal epithelium and show that host IFN signaling controls replication in an IFN-specific manner.
最近全球肠道病毒 71 型（EV71）的爆发导致了手足口病的重大流行，伴有严重的神经并发症，包括急性弛缓性麻痹。EV71 通过肠内途径传播，但人们对其穿过人体胃肠道的机制知之甚少。我们使用原代人肠道上皮细胞单层，表明 EV71 从顶端表面感染上皮细胞，在该处它优先感染杯状细胞。我们发现 EV71 感染不会改变上皮屏障功能，但确实会降低杯状细胞衍生粘蛋白的表达，这表明它改变了杯状细胞的功能。我们还表明，肠道上皮细胞通过选择性诱导 III 型干扰素（IFN）来对 EV71 感染做出反应，从而限制 EV71 的复制。总的来说，这些发现定义了与人类肠道上皮细胞中 EV71 感染相关的早期事件，并表明宿主 IFN 信号以 IFN 特异性方式控制复制。
